Skip to main content
  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

AACR logo

  • Register
  • Log in
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Cancer Immunology Essentials
    • Collections
      • COVID-19 & Cancer Resource Center
      • Toolbox: Coding and Computation
      • Toolbox: Signatures and Cells
      • "Best of" Collection
      • Editors' Picks
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in
  • My Cart

Search

  • Advanced search
Cancer Immunology Research
Cancer Immunology Research
  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Cancer Immunology Essentials
    • Collections
      • COVID-19 & Cancer Resource Center
      • Toolbox: Coding and Computation
      • Toolbox: Signatures and Cells
      • "Best of" Collection
      • Editors' Picks
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

Tackling the Tumor Microenvironment: Beyond T-cells

Abstract A060: Targeting glioma-macrophage interplay via LOX in PTEN-deficient glioblastoma

Peiwen Chen, Alan Wang and Ronald DePinho
Peiwen Chen
University of Texas MD Anderson Cancer Center, Houston, TX.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alan Wang
University of Texas MD Anderson Cancer Center, Houston, TX.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ronald DePinho
University of Texas MD Anderson Cancer Center, Houston, TX.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/2326-6074.CRICIMTEATIAACR18-A060 Published February 2019
  • Article
  • Info & Metrics
Loading
Abstracts: Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; September 30 - October 3, 2018; New York, NY

Abstract

Glioblastoma multiforme (GBM) is the most lethal form of brain cancer in adults. The median survival of GBM patients is only about one year after initial diagnosis. Genomic profiling has stratified GBM into various subgroups, which are driven by specific genetic alternations of core signaling pathways, including RTK/RAS/PI3K/PTEN, P53/ARF/MDM2 and RB/CDKN2A pathways. However, targeted therapies, such as therapy against EGFR, have failed in the clinic, and no effective therapeutic drugs are available to target tumor suppressors. A key reason for therapeutic failure is inter- and intra-tumoral cancer cell genetic instability and heterogeneity, resulting in aberrant activation of multiple signaling pathways within and across tumors. Stromal/immune cells in the tumor microenvironment (TME) are genetically stable, which not only play a pivotal role in GBM progression by affecting multiple cancer hallmarks, but can also be educated by cancer cells. However, whether and how the behavior and function of specific stromal/immune cells in the TME are regulated by cancer cell with specific genetic alterations in GBM remain relatively undefined. Utilizing a large scale of bioinformatic analysis in TCGA GBM patients, we revealed that genetic alteration (deletion/mutation) of PTEN in GBM patients specifically triggers immune response by promoting macrophage recruitment, without affecting macroglia and other immune cells. Using unbiased transcriptome profiling following functional validation, we identified that lysyl oxidase (LOX) is preferentially secreted by PTEN-deficient cancer cells. In vitro transwell migration assay and in vivo Matrigel Plug assay demonstrated that LOX is a potent macrophage chemoattractant. Transcriptome profiling following Gene Set Enrichment Analysis (GSEA) and functional validation demonstrated that activation of SRC and AKT signaling pathways drives LOX upregulation in PTEN-deficient cancer cells. Genetic and pharmacologic inhibition of LOX in PTEN-deficient cancer cells does not affect tumor cell proliferation in vitro, but markedly inhibits macrophage density and tumor growth in vivo. Using the bioinformatics analysis in clinical GBM samples, we demonstrated that LOX is enriched in GBM patients with higher macrophage density, and that these patients show lower survival. Together, our findings highlight the significance of PTEN-LOX axis in macrophage infiltration in GBM, and demonstrate a possibility of improving GBM treatment by targeting this axis-mediated macrophage recruitment.

Citation Format: Peiwen Chen, Alan Wang, Ronald DePinho. Targeting glioma-macrophage interplay via LOX in PTEN-deficient glioblastoma [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A060.

  • ©2019 American Association for Cancer Research.
Previous
Back to top
Cancer Immunology Research: 7 (2 Supplement)
February 2019
Volume 7, Issue 2 Supplement
  • Table of Contents

Sign up for alerts

Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Immunology Research article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Abstract A060: Targeting glioma-macrophage interplay via LOX in PTEN-deficient glioblastoma
(Your Name) has forwarded a page to you from Cancer Immunology Research
(Your Name) thought you would be interested in this article in Cancer Immunology Research.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Abstract A060: Targeting glioma-macrophage interplay via LOX in PTEN-deficient glioblastoma
Peiwen Chen, Alan Wang and Ronald DePinho
Cancer Immunol Res February 1 2019 (7) (2 Supplement) A060; DOI: 10.1158/2326-6074.CRICIMTEATIAACR18-A060

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Abstract A060: Targeting glioma-macrophage interplay via LOX in PTEN-deficient glioblastoma
Peiwen Chen, Alan Wang and Ronald DePinho
Cancer Immunol Res February 1 2019 (7) (2 Supplement) A060; DOI: 10.1158/2326-6074.CRICIMTEATIAACR18-A060
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Info & Metrics
Advertisement

Related Articles

Cited By...

More in this TOC Section

Tackling the Tumor Microenvironment: Beyond T-cells

  • Abstract A106: Higher numbers of cancer stem cells in the peripheral blood of children with B-ALL after chemotherapy
  • Abstract A089: The effect of lactate dehydrogenase-A (LDH-A) knockdown and human prostate-specific membrane antigen (hPSMA) directed CAR T-cell treatment on hPSMA(+) Myc-CaP tumors
  • Abstract IA07: Using matrix protein affinity to modulate the tumor microenvironment
Show more Tackling the Tumor Microenvironment: Beyond T-cells

Tackling the Tumor Microenvironment: Beyond T-cells: Poster Presentations - Proffered Abstracts

  • Abstract A106: Higher numbers of cancer stem cells in the peripheral blood of children with B-ALL after chemotherapy
  • Abstract A089: The effect of lactate dehydrogenase-A (LDH-A) knockdown and human prostate-specific membrane antigen (hPSMA) directed CAR T-cell treatment on hPSMA(+) Myc-CaP tumors
  • Abstract IA07: Using matrix protein affinity to modulate the tumor microenvironment
Show more Tackling the Tumor Microenvironment: Beyond T-cells: Poster Presentations - Proffered Abstracts
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook   Twitter   LinkedIn   YouTube   RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Cancer Immunology Essentials

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians

About Cancer Immunology Research

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2021 by the American Association for Cancer Research.

Cancer Immunology Research
eISSN: 2326-6074
ISSN: 2326-6066

Advertisement